While evaluating mouse-derived anthelmintic leads against gastrointestinal nematodes of sheep, a precursor compound of pyrantel containing sulfur in a side chain was tested in Terra Haute. Scheme 62. This ability of plants and animals to readily convert inactive precursors into goitrogenic agents must be considered when the possible etiological role of dietary elements in endemic goiter is being investigated. However, reversible kidney toxicity was observed in this study, detected by increased creatinine levels in treated subjects and attributed to renal tubular dysfunction, toxicity concerns that prevented further development of the compound, which was terminated in Feb. 2007.272, P. Mátyus, P. Tapolcsányi, in Comprehensive Heterocyclic Chemistry III, 2008. The hepta-N,O-acetyl derivative d-404 fully supported the structures assigned for d-403 (Scheme 52).118. Thus, the drug not only binds irreversibly to amino groups of amino acids and proteins to form thiourea derivatives [99], but may also inhibit the activity of various enzymes catalysed by thiols. This ring system could be prepared by thionation of benzil monohydrazone 172 with Lawesson’s reagent (LR) followed by cyclization. Some maleimides (e.g., pyrene and stilbene derivatives) have very low fluorescence until after conjugation with thiols to form fluorescent adducts useful for thiol quantitation and for their semiquantitative localization in cellular organelles. 1). Isothiocyanates are widely used to label proteins to form thiourea derivatives for fluorescence microscopy and fluorescence immunoassays. Scheme 61. (a) 2% HCl in MeOH, 50 °C, 2 h; then added Et3N, rt, 2 h, 89%; (b) MeCN, 2-chloro-3-ethylbenzoxazolium tetrafluoroborate, 0 °C under N2, 1 h; then added Et3N, 30 min, 84%; (c) MeOH, Pd(OH)2 on carbon, H2, 60 °C, 30 min, 46%. Removal of the benzyl groups from 424 by hydrogenolysis gave 416 in 42% yield. (a) Et3N, 69%; (b) EtBF4, Et3N, 68%; (c) H2, Pd(OH)2 on C, 44%. Thioglycosides undergo a rearrangement to form isothiocyanate derivatives and, in some instances, thiocyanate. After it was administered to sheep, the barn, environs, field hands, and laboratory personnel became unwittingly exposed to a highly disagreeable odor. Figure 24. Photosensitized electron transfer cyclization of compound 173 to pyridazinooxadiazine 160 by UV irradiation in the presence of 1,4-dicyanonaphthalene (DCN) and methyl viologen (MV) was carried out. New compounds, lacking the aliphatic sulfur (and the disagreeable odor) were prepared. Figure 3. System... Crystalline meta-substituted aromatic bis(thiourea) derivatives adopt either cyclic dimeric or extended three-dimensional network structures through efficient and extensive hydrogen bonding. Therefore, the amount of thiocyanate in the urine is a good indicator of the presence of thioglycosides in food. Working off-campus? Thiocyanate is also found in high concentrations (1 g/L) in wastewater effluents of coal conversion processes and in body fluids as a metabolite of hydrogen cyanide gas consumed while smoking. 95–98 In 1998, Jacobsen and coworkers reported the first efficient chiral organocatalyst bearing thiourea unit for the asymmetric hydrocyanation of imines (the Strecker reaction). The thiol functional group is not very common in most proteins. In more detailed mechanism of action studies, ACH-806 (96) had no effect on polyprotein processing or NS5B polymerase activity but reduced the amount of NS3 and NS4A in replicons, attributed to an accelerated degradation that resulted in an altered composition of the replication complex.272,273 ACH-806 (96) treatment led to the appearance of a 14 kDa protein determined to be a dimer of NS4A, while an analog containing an azide photoaffinity element selectively labeled NS4A. Scheme 11. However, the stereoconvergence could be observed by adding a catalytic amount of PPh3 (triphenylphosphine) with (R)-61 as the major product. Cassava, a staple food in these areas, has antithyroid effects in humans and experimental animals. The activities of this trehazolin β anomer (433) toward two trehalases were found to be much weaker than that of natural trehazolin (2).119. Chitosan is effective at removing platinum from dilute solutions, but sorption properties are significantly affected by the presence of competitor anions, such as chloride and, especially, sulfate anions. Aldehydes can react with primary amines to form Schiff bases. Scheme 52. (a) 75% aq. Treatment of the acetoxyimino derivative 171 with K2CO3 as the base in DMF gave the tricyclic compound 157 in low yield; the intermediate 172 was also isolated (Equation 25) <2000JHC297>. Nitroscanate (32b) inhibits ATP synthesis in the liver flukes, Fasciola hepatica[105]. The thiourea derivative that showed the greatest frequency shift in the QCM experiment was TU13 which has 3,5-bis-(trifluoromethyl)phenyl as one N-substituent and (CH 2) 3-phenyl as the other N-substituent. Removal of the benzyl groups from the glucosylamine derivative 420 was accomplished by hydrogenolysis with Pd(OH)2 on carbon to give the trehalostatin analogue 416 in 37% yield (Scheme 57).106,107. Plausible mode of activation of the substrates using thiourea-amine catalyst. Thiourea derivatives are known to accelerate certain reactions such as radical cyclization and the addition of tetramethylsilylcyanide to nitrones via hydrogen-bonding. Scheme 50. Additionally, isothiuronium chloride attached to a polymer matrix donates the C–N fragment for the 1,2,4-triazine ring in a solid-phase reaction with 2,3-diaza-3-pentenedionic anhydride to give 3-amino-1,2,4-triazinones 261 in 50–74% yields (Scheme 154) <2001TL4433>. Subsequently, List and co-workers successfully realized the ATH reactions of β-nitroacrylates 58 using almost identical reaction conditions to the aforementioned analogous reactions of unfunctionalized trisubstituted nitroolefins.17b These β-nitroacrylates could be easily prepared by first condensing α-ketoester with nitromethane followed by dehydrating the resulting alcohols in acidic condition.